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Study of biological molecules in hair follicle in patients with alopecia Areata
References:
1. Ag-ool E. M. The influence of social-hygienic, ecological factors to the state of health and physical development of pupils of the Republic of Tiva.//Hygiene and sanitation - М., 2007. - № 5. - P. 64-67.
2. Giguz T. L., Polyakov A. Ya., Bogachanov N. D. Dynamics of physical development of school children in Novosibirsk.//Hy-giene and sanitation - М., 2007. - № 4. - P. 50-52.
3. Isaac S. I., Panasyuk T. V Characteristics of physical development of school children of different regions of Russia.//Hy-giene and sanitation. - М., 2005. - № 5. - P. 61-64.
4. Povargo E. A., Zigitbayev R. N., Shubina Kh. Z. and others. The main trends in physical development of junior school children.//Hygiene and sanitation. - М., 2007. - № 2. - P. 71-73.
5. Chmil I. B., Medvedev L. N. Age dynamics of anthropometric indexes of children of Krashoyarsk.//Hygiene and sanitation. - М., 2002. - № 2. - P. 49-51.
Azimova Fatima Vakhidovna, Senior staff scientist of Republican Specialized Science Practical Medical Center of Dermatology & Venereology,
Republic of Uzbekistan E-mail: [email protected]
Study of biological molecules in hair follicle in patients with alopecia Areata
Abstract: The given article is devoted to studying factor of growth of fibroblasts (bFGF) and factor of apoptosis (FasL) in patients with alopecia areata. Concentration of factor of growth of fibroblasts bFGF in blood is reliably decreased, and concentration of factor of apoptosis FasL is reliably increased in patients with alopecia areata. Indications of factors of growth and apoptosis observed correlate with grade of disease severity and indicate a fine regulation of phases of vital cycle of hair follicles of proteins of families FGF and FasL.
Keywords: alopecia, cytokins, dermatoscopy.
At present an incidence rate of a number of able-bodied patients is noted referring to physicians with problem of hair shedding. Besides, a tendency to an incidence growth of torpid elapsing forms of disease resistant to the therapy conducted. Demography investigations showed that 0.05-0.1 % population is exposing alopecia at least once during its life. The first signs of alopecia are showing up in the majority of people aged 15-30. At the same time cases of registration of alopecia areata in children of tender years became more frequent, especially that of taeniate and universal forms. All above-stated evidenced both medical and social significance of a problem discussed [1].
Alopecia areata occurred rather often in the last time and is characterized by baldness nidi on the hair-covering area of head, eyebrows, beard or trunk. It was established that development of alopecia takes place against a background of numerous causes to which belong combination of alopecia circumscripta and autoimmune diseases, genetic predisposition, weak type of nervous system, nidi of focal infection (tonsillitis, pharyngitis, helminthic invasion, inflammation of bile ducts and other chronic inflammatory processes in organism), and familial cases of morbidity. In spite of a great number of the performed studies many questions of etiology and pathogenesis of alopecia remain insufficiently explored. At the same time effectiveness of different therapeutic
methods varies in wide limits, and results of treatment do not always satisfy both clinicians and patients. Hereupon the performing modern immunogenetic, histochemic investigations allowed to explore deeper pathogenetic mechanisms of development of various alopecia forms [2; 5].
At present an interest of many scientists is directed towards studying mechanisms and factors of intercellular interaction of different alopecia forms, main ofwhich are adhesive cellular molecules, molecules of extracellular matrix, cytokins [4; 11]. Cytokins are high-potent hormone-like proteins that are synthesized by different cellular species. Cytokins are divided in the following classes: 1) interleukins; 2) interferons; cytotoxins; 3) hemopoietic colony-stimulating factors; 4) growth factors; 5) inhibiting factors. One of the valuable cytokins are growth factors, representing proteins molecules (molecular weight from 5 000 up to 50 000 daltons), stimulating or inhibiting division or differentiation of various cells and being main transporters of mitogen cellular signal. Growth factors are related with tyrosine kinase receptors on cellular surface that provides dimerization and activation of the latter. Phosphorylation cascade is initiating and as biologic effect of phosphorylation manifested intensification of mitogen characteristics of tissues and differentiation of cells, stimulation of transport systems and chemotaxis, activation of metabolic pathways [6; 12]. Because of the main cellular
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Section 8. Medical science
origins of dermal papillae are fibroblasts, an interest study is study of fibroblast’ growth factor (FGF), as well as a factor of apoptosis in patients with different forms of alopecia areata and effect of these molecules on growth (anagen) and rest (telogen) phases of hair follicle.
It is known that 22 factors were identified in humans. These factors belong to the family of growth factors of fibroblasts (FGF), expressing in skin, and 4 receptor’ forms to them. They can differently directed effect on a state of hair follicle contributing to stimulation of growth or, on the contrary, entry of hair into stage ofperiod of telogen, i. e. family FGF accomplishes fine regulation of replacement of periods of active growth, rest and shedding of hair. American scientists detected that expression activity of mRNA in different FGF depends upon a cycle phase. So, expression of mRNA FGF 18 and 13 achieves its maximum in period telogen, FGF 7, 10, 5 and 22 — in the second half of anagen. In a culture FGF 18 stimulates synthesis of DNA in human dermal fibroblasts, cells of dermal papillae, epidermal keratinocytes and vascular endotheliocytes. In hypodermic administration of GF 18 to mice which hair follicles are in a phase of telogen it was observed their transformation into phase of anagen with activation of hair growth [7; 8; 10]. One of the most studied and already used in Dermatology and Com-bustiology of FGF is FGF-2, or the basic bFGF growth factor of fibroblasts. FGF-2 is able to work intracellularly as activator of proliferation. It positively effects on a growth of all the types of dermal cells, stimulates components’ production of extracellular matrix by fibroblasts, stimulates their chemotaxis and synthetic activity. Possibility of synergism between VEGF and bFGF in induction of angiogenesis detected to be in studies in vitro, including perifollicular area during anagen [6; 9]. It was proved in a whole number of experimental works that addition of dermal papillae cells of bFGF to cultural medium sufficiently increases their activity and gives rise to hair growth. Subcutaneous administration of gelatin hydro gel containing bFGF resulted in increasing area and length of hair in a zone of administration, whereas pure hydro gel (without growth factors) didn’t have such an effect of hair growth. It was established that concentration ofbFGF is especially high in areas ofproliferation of the developing and mature follicles that evidenced its role of regulator of cellular mitotic activity of epithelial origin. On the contrary, FGF1 presents in differentiated cells of hair bulbs, where it may take part in formation of structural components of follicles or fibers. It was exhibited in vitro that bFGF postpones approaches of katagen in cellular culture of hair follicles, whereas aFGF acts as promoter of katagen [3].
Aim of study: Investigation of growth factor of fibroblasts bFGF and apoptosis factor FasLy in patients with alopecia areata aimed at improvement of therapy of the given disease.
Materials and methods of study: Ninety-eight patients suffering from various forms of alopecia areata, receiving ambulance and hospital treatment in the Republican Specialized Science Practical Medical Center of Dermatology & Venereology, Ministry of Public Health, Republic of Uzbekistan were under our observation. All the patients were aged from 19
to 42, males were 43.3 %, females — 56.7 %. Circumscribed form of alopecia areata — focal and polyfocal was noted in 58.2 % patients, distributed form — subtotal and total — in 29.6 % and universal form — in 12.2 % patients. Duration of disease in 12.4 % patients was up to 1 year, in 26.2 % — from 1 to 5 years, in 61.4 % — up to 10 years and over. The progressing stage of disease with “zone of shaking hair" on the periphery of foci of shedding hair was registered in all the patients with alopecia areata. Control group consisted of 15 individuals not suffering from alopecia areata, representative in their age and sex. Factor of growth of fibroblasts bFGF and factor of apoptosis FasL were studied in blood of patients with alopecia areata and health individuals of control group by polarization fluoroimmunoassay (ELISA) method with using of test-system of Sigma firm (Germany).
Trichodermatoscopy of skin of hair-covered part of head was conducted in all the patients. So, trichoscopy examination under lens X60 in patients with alopecia areata, polyfocal and subtotal forms of alopecia areata showed decrease in hair density both in parietal and occipital parts of head — 125-163 (norm 235) and 112-175 (norm 213) hair cm 2 (square centimeter), increase of a number of wool hairs up to 56 % in parietal area and up to 71 % — in occipital area and, accordingly, decrease of a number of the growing terminal hairs up to 44 % in parietal and up to 29 % in occipital areas. Medical examination of damage foci revealed cadaveric hairs, pathologic hairs as exclamation marks and hair-free follicles ofdifferent atrophy degrees. Subtrophic and further atrophic hair follicles were fixed in patients with total and universal forms of alopecia areata equally with single cadaveric hairs. Dystrophic and dysplastic roots of anagen hairs were observed in examination by lens X200 hair roots round foci of hair shedding and in zone of hair.
Results of investigation: How it is seen from the table 1, concentration of factor of growth of fibroblasts bFGF in blood of patients with alopecia areata is high reliably decreased as compared with analogous indications of control group, whereas such reduction correlates with severity degree of disease and the most lower indications of the given factor were observed in patients with severe universal form of disease. So, concentration of factor of growth of fibroblasts was 90.0 ± 5.38 pg/ml in patients with focal and polyfocal forms of alopecia areata, with subtotal and total forms — 65.6 ± 7.38 pg/ml, with universal form — 44.3 ± 9.64 pg/ml, whereas an analogous index of control group was 217 ± 12 pg/ml.
Thereupon factors of growth play a key role in proliferation, migration and angiogenesis of cells of hair follicle a decrease of factor of growth of fibroblasts in patients with alopecia areata shows not only inhibition of proliferative processes in dermal papilla of hair follicle and an early transition of papilla from a stage of anagen into a stage of telogen but also defined degrade changes in dermal papillae. Inhibition of proliferative processes in dermal papilla in patients with alopecia areata was proved by a certain increase of concentration of apoptosis factors of growth. So, a reliable increase of factor of apoptosis FasL observed to be in patients with alopecia areata,
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Treatment of diaphyseal fractures of the metacarpal bones
and the given indicator was sharply increased with increase of severity of disease. Factor of apoptosis FasL in focal and polyfocal forms of alopecia areata was 0.9 ± 0.19 pg/ml, subtotal and total forms — 2.42 ± 0.16 pg/ml, universal form — 2.97 ± 0.32 pg/ml, whereas factor of apoptosis FasL in control group was 0.036 ± 0.01 pg/ml.
Conclusions: Thus, studies carried out permit to conclude that proteins of families FGF and FasL are responsible for a fine regulation of phases of vital cycle of hair follicles. It is possible that studies aimed at regulation of concentration of these proteins in hair follicles in alopecia areata form a basis for improvement of therapy of the given disease.
References:
1. Adaskevich V. P., Myadelets О. D., Tikhonovskaya I. V. Alopecia. - М., 2000.
2. Gajigoroyeva А. G. Hair diseases: classification. Non cicatricial alopeciae.//Dermatology, 2008. - 1.
3. Zarudiy R. F., Ahmerov R. R. Electron journal “Regenerative Surgery”, UDC 616.5-085:615.38. - 2005. - № 3.
4. Mazitova L. Effect of endocrine, metabolic and chemical factors on hairs shedding and their structure in women. Les Nouvelles Esthetiques. - Russian Edition, 2002. - 1. - P. 40-42.
5. Tkachev V. P. Trichology. Lecture of the course of thematic improvement. - ФПК МР РУДН, 2008.
6. Yano K., Brown L. F., Detmar M. Control of hair growth and follicle size by VEGF-mediated angiogenesis. Clinical Investigation, 2001. - 107 (4). - P. 409-417.
7. Boo Y., et al. Shear Stress Stimulates Phosphorylation of Endothelial Nitric-oxide Synthase at Ser1179 by Akt-independent Mechanisms.//The Journal of Biological Chemistry. - 2002. - 277. - P. 3388-3396.
8. Witzel S. et al. Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane.// Journal of Cell Biology. - 2006. - 175 (5). - P. 791-802.
9. Hoeben A., et al. Vascular endothelial growth factor and angiogenesis.//Pharmacology Review. - 2004. - 56. - P. 549-80.
10. Colombe L., Michelet J. F., Bernard B. A. Prostanoid receptors in anagen human hair follicles.//Experimental Dermatology. - 2008. - 17 (1). - P. 63-72.
11. Happle R. Diphencyprone for the Treatment ofAlopecia Areata - More Data and New Aspects. Archives of Dermatology, 2002. - 138. - P. 112-113.
12. Verbaan F. J. Assembled micro-needle arrays enhance the transport of compounds varying over a large range of molecular weight across human dermatoid skin.//Journal of Controlled Release. - 2007. - 117 (2). - P. 238-245.
Khaydarov Azizjon Kosimovich, Tashkent Medical Academy, Republic of Uzbekistan E-mail: [email protected]
Treatment of diaphyseal fractures of the metacarpal bones
Abstract: It was presented the experience of theapplication of stable osteosynthesisby three Kirschner wires on diaphyseal fractures of the metacarpal bones on 74 patients. Indications for osteosynthesiswere opened (6 %), closed (94 %), non-united, mal-unitedfracturesand false joints of metacarpal bonesdiaphysis. Patients were performed intraosseous anesthesia atdistalepimetaphysisarea of radial bone anddescribeda method of operation extra-medullaryosteosynthesis using three Kirschner wires. Also, describedmethod of wedge osteotomy for full recovery of hand function. Good results were obtained in 83.1 % of patients, satisfactory at 13.6 %, and unsatisfactory results in 3.4 % of patients.
Keywords: metacarpal bones, wedge osteotomy, diaphys , fracture.
Introduction
Treatment of fractures of the metacarpal bones isstilla difficult part of Hand Surgery. At the recent time, there is no singleapproach to the choice of treatment for different diaphyseal fractures of the metacarpal bones. Conservative treatment is not always sufficient retention for consolidation of bone fragments and often leads to secondary fragments-displacement after reduction.
Basically among surgeries used intra and extramedullary-ostesinthesis alsoextrafocalexternal fixation and diafixation-
method. Intramedullary osteosynthesis pin allows for reliable fixation of fragments, provides extra-articular holding metal fixating contributes less traumatizationinterosseal muscles and longitudinal arch brush, can be apply for multiple fractures of metacarpal bones. The disadvantage is the inability to intramedullary nailing accurate repositioning of the high rigidity and bending pin curvature mismatch metacarpal bone and the complexity of its removal after bone fragmentsconsolidation. As extramedullary stable osteosynthesis of tubular bones of the hand has been used successfully mono-local extramedullary
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